Management for Refractory Reflux

Thursday, November 12, 2009

• Approximately 10-20% of patients with gastroesophageal reflux symptoms do not respond to once-daily doses of proton pump inhibitors, and 5% do not respond to twice-daily doses [22].
• These patients undergo endoscopy prior to escalation of therapy. The presence of active erosive esophagitis usually is indicative of inadequate acid suppression and can almost always be treated successfully with higher proton pump inhibitor doses (eg, omeprazole 40 mg twice daily) [22] .
• Truly refractory esophagitis may be caused by gastrinoma with gastric acid hypersecretion (Zollinger-Ellison syndrome), pill-induced esophagitis, resistance to proton pump inhibitors, and medical noncompliance [22] .
• Patients without endoscopically visible esophagitis should undergo esophageal pH monitoring to determine the amount of esophageal acid reflux and to assess whether the symptoms are acid related.
• If the pH study shows a normal amount of acid reflux, treatment with a low-dose tricyclic antidepressant (eg, imipramine or nortriptyline 25 mg at bedtime) may be beneficial [22].
• As second-line therapy of refractory heartburn with or without esophagitis, standard-dose H2RA therapy for an additional 2 to 4 weeks produces a limited increase in the cumulative rate of heartburn resolution (range of increase, 2 to 8%).
• For refractory erosive reflux esophagitis, extending the duration of treatment by 4 to 12 weeks with standard-dose H2RA produces modest increases in cumulative healing rates (median increase, 14%; range, 13 to 21%).
• Patients with erosive esophagitis or worse should be treated with proton pump inhibitors (PPI) in a double therapeutic dose.
• If Esomeprazole (Nexium®) has not been used at this point, it would be reasonable to try a therapeutic trial.
• Patients intolerant of PPIs may receive a quadruple therapeutic dose of H2RA. Failure to respond should prompt doubling the dose of the antisecretory medication and referral to gastroenterology

• There are several indications for surgery in the patient with GERD [14]:

Persistent or recurrent symptoms despite medical therapy
Severe esophagitis by endoscopy
Benign stricture
Barrett's columnar-lined epithelium (without severe dysplasia or carcinoma)
Recurrent pulmonary symptoms (eg, aspiration, pneumonia) in association with GERD
• Different endoscopic techniques have been developed to treat chronic GERD on an outpatient basis since PPI therapy is expensive and not curative [19].
• In general these techniques use three different approaches to improve the function of the gastroesophageal barrier. The gastroesophageal junction can be tightened either by the delivery of radiofrequency-energy at the cardia with the Stretta procedure, by the creation of plications with the Full-Thickness Plicator or Endocinch, or by the injection/implantation of inert material into the wall with the Gatekeeper or Enteryx procedures [20].

Single Trial Step-Down Therapy
• All patients with GERD should have one attempt at discontinuation therapy.
• Step-down therapy gradually reduces the intensity of treatment as tolerated to maintain the patient in remission.
• Changes should be made at 2 – 4 weekly intervals
• Lifestyle modifications should be continued indefinitely. Patients whose initial symptoms were controlled by lifestyle measures initially may require only occasional PPIs.
MAINTENANCE THERAPY —
• Given the propensity of esophagitis to relapse, maintenance acid suppressive therapy is often necessary [15]
• After discontinuation of proton pump inhibitor therapy, relapse of symptoms occurs in 80% of patients within 1 year the majority of relapses occurring within the first 3 months. [1]
• The need for maintenance therapy depends largely on the severity of the disease and the persistence of symptoms after the withdrawal of initial pharmacologic therapy [15].
• If the symptoms relapse in < 3 months and endoscopy has not been done, advise endoscopy and H Pylori testing
• If no H Pylori infection and GERD proven on endoscopy, treat with previously effective treatment indefinitely.
• If symptoms relapse in > 3 months repeat course of previously effective acute treatment indefinitely [1]
• In most patients with mild symptoms, antacids or over-the-counter H2-receptor blockers can be used as needed to help control symptoms.
• The lowest effective scheduled dosage of an H2-receptor blocker or a prokinetic agent should be used in patients with nonerosive esophagitis and moderate to severe symptoms.
• Patients with erosive esophagitis or complicated disease should be given one of the proton pump inhibitors because of the higher rates of remission associated with these agents [15].
• The lowest effective dosage should be used to maintain remission
• Maintenance therapy should be continued for 3 – 6 months
DRUG SAFETY
With maintenance antisecretory therapy being the rule rather than the exception, drug safety becomes an important issue. Various problems that can arise due to long term acid suppression are [24]:
1. - Pneumonia
2. - Hypergastrinemia
3. - Atrophic gastritis
4. - Enteric infections
5. - Vitamin B12 malabsorption

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